Pathology is regarded as the key to the understanding of disease mechanism. Research on post-mortem brain tissue is particularly important for neurological diseases, many of which are complex and poorly understood. Notwithstanding the remarkable advances in neuroimaging and genetics, our knowledge of common neurological conditions such as multiple sclerosis, dementia and Parkinson’s disease continues to be underpinned by their pathological identities, which were established by meticulous brain tissue research. Disease-specific national brain banks have contributed significantly in this research and in the past decade, data from brain pathology have been used to refine criteria for clinical diagnosis, evaluate disease-specific biomarkers and identify novel therapeutic targets.

At present, the diagnosis of chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is essentially clinical and there is no proven disease-specific biomarker. Clinical experience suggests that overwhelming fatigue, and in many cases, chronic pain that characterise and disable CFS/ME patients, are central, i.e., brain-derived and that these patients are distinct from psychiatric patients who may also report chronic fatigue and pain. Distinguishing appropriately defined CFS/ME patients from psychiatric patients is important for many reasons, not the least because treatment options and prognosis may differ.

In an autopsy study of two young patients with a life-time diagnosis of CFS/ME, we discovered unequivocal tissue changes supportive of an underlying neuropathology in these cases which, although not identical, were sufficiently distinct from normal or depressed cases. We propose that research on brain tissue would be essential to establish the clinical identity and pathological signatures of CFS/ME. National brain banks for CFS/ME, similar to other neurological diseases, would be a necessary step to move the research forward through international collaboration.